3-Thiochromanone

The fixed geometry of a, 3-unsaturated ketones in the S-cis form, as observed in arylidene alkanones, influences their reactivity. For example, the reaction of arylhydrazines with 3,5-diarylidene-4-piperidones, 2-arylidene-l-tetralones, 2,6-diarylidenecyclohexanones and 2-arylideneindan-l,3-diones requires stronger conditions than for the case of their noncyclic analogues [76, 77, 78, 79, 80, 81, 82, 83, 84]. However, arylidene derivatives of cyclohexanone, 1-indanone, 4-chromanone, 4-thiochromanone and TV-methyl-4-piperidone hydrochloride react with hydrazines more easily [85,86,87,88], It is interesting to note that the more complicated and sterically hindered unsaturated ketones of the spiro type 64 react with hydrazine and phenylhydrazine very easily in the presence of piperidine, leading to pyrazoles 65 in high yields [89] (Scheme 2.16). 

Condensation of 2,2-dimethoxy-l-methyl pyrrolidine(piperidine) with 1-indanone, 1-tetralone, 4-thiochromanone, butyrolactone, phthalide and substituted 2-oxindoles gives the corresponding enaminoketones614. 

Thioxanthenes are not only valuable synthetic intermediates [1], they also find considerable interest in pharmaceutical research [2] and as dyes for numerous applications [3]. Only few methods are known for the stereoselective synthesis of S-heterocycles [4], Sequential transformations are a powerful strategy in organic synthesis frequently allowing the synthesis of complex molecules in a single synthetic operation [5]. It was anticipated that 4-silyloxy-l-benzothiopyrylium-salts 1 [6], which represent double-activated 4-thiochromanones, can be used for the stereoselective synthesis of aimulated thiochromanones 3 by reaction with 2-silyloxy-l,3-butadienes 2 [7]. 

A variety of /S-chlorovinylaldehydes are obtained in the reaction of acetophenones, p-acetylbiphenyl, deoxybenzoin, acetonaphthenone, 4-chromanone, 4-thiochromanone, 5-tetrahydrobenzoxepinone, 5-tetrahydro-benzothiepinone (Weissenfels et al. report yields of 24-80%), and p-diacetyl-benzene with the DMF-POas complex... 

Photolysis of 2-azido-4-thiochromanone 1,1-dioxide afforded the ring-expanded product (118), while (119) and (120) were formed by base-catalysed sulphimide rearrangements. 

Thiochromanones, on photolysis (350 nm) in methanol, undergo not photoisomerization, such as is observed with 4-isothiochromanones, but photodehydrogenation to 4-thiochromones in moderate (50—55%) yield. 2-(t-Butylthio)-benzaldehyde (177), prepared in near quantitative yield from 0-nitrobenzaldehyde as indicated in Scheme 40, is a useful new synthon for thiocoumarins (178 R = CO2H, CONH2, C02Et, CN, Bz, Ph, or 2-thienyl) and benzo[l,2-f> 5,4-f> ]bisthiopyrans (179). ... 

The thionation-cycloaddition sequence is accompanied by the elimination of dimethylamine from the cycloadduct to afford thiopyrans. Similarly, when the thionation-cycloaddition methodology was applied to enaminoketones 98 and 99, obtained from thiochromanones, tricyclic compounds 100 and 101 were obtained (Figure 2.12). 

Treatment of dibromides 2 with sodium azide in N,N-dimethylformamide (DMF) at room temperature resulted in the formation of two products, 3-(a-azidobenzyOchromones 2a-c,g or -1-thiochromones 2d-f and the 3-arylidenechromanones la-c,g,h or -1-thiochromanones Id-f, respectively (eqn. 2). As shown by yield data given in Table 2, the substituent at position 2 plays decisive role in the product ratio. Dibromides unsubstituted at position 2 tended to give almost exclusively azides 3a-f and only a small amount of 1 was obtained. On the contrary, the reaction of flavanone derivatives 2gjh gave 3-arylideneflavanones... 

Of the many substituted and functionalized alkenes that have been combined with diazo dipoles to give A -pyrazolines or products derived from them (i.e., A -pyrazolines, pyrazoles, cyclopropanes), only a selection will be mentioned. These include ot-alkylidene-cycloalkanones (62), -flavanones, -thioflavanones, -chroma-nones, and thiochromanones (63,64) a-arylidene-indanones and -indolones (65) diarylideneacetones (66) l-benzopyran-2(77)-ones (coumarins) (67,68) 4-nitro-1,2-oxazoles (69) 2-alkylidene-2-cyanoacetates (70) dimethyl 2,3-dicyanofuma-rate (71) tetracyanoethylene (72) tetraethyl ethylenetetracarboxylate (72) 1,4-quinones (35,73-75) 2-X-l,l,l-trifluoro-2-propene [X = Br, (76), SPh, SOPh, S02Ph (77)] nitroalkenes (78) including sugar nitroalkenes (79) 1-diethoxyphos-phoryl-1-alkenyl-sulfoxides (80) methyl 2-(acetylamino)cinnamate and -acrylate... 

The scarcity of reviews1 and recent interest in thiochromanones and related compounds calls for a comprehensive summary of this area of heterocyclic chemistry. The apparent similarity between these systems and the naturally occurring chromanones, chromones (flavones), chromenes, etc., is responsible for the continued importance of these sulfur heterocycles. Chemical Abstracts (through November, 1973) has been employed as the principal reference source and nomenclature guide for this review. 

Further synthetic entries into the thiochromanone ring system have involved arylmercaptosuccinic acids20,21 (10) as in Eq. (3) and the reaction of ethyl o-mercaptobenzoates with 2,3-diene carbonitriles22 as in Eq. (4). 3-Substituted thiochromanones (12) are prepared by the... 

Halogenation of thiochromanones is a fruitful entry into other systems. As shown in Scheme 2, bromination of 6-methylthiochroman-4-one produces the perbromide (22), converted by water into the sulfoxide (23). Upon standing, 22 loses hydrogen bromide to form the 3-bromo compound (24), which yields the 3-amino analog and 6-methylthiochrom-4-one with ammonia and dimethylaniline, respectively.43-44... 

Bromothiochroman-4-ones are generally ring opened by hydroxide to thiosalicylic acids,45 with formaldehyde they yield the corresponding 3-epoxy system (25) which can be converted into the 3-hydroxymethyl isomer (26).46 Attempts to convert 25 into benzothiepins via acid-mediated ring expansions have failed, yielding thiochromanones instead.47,48... 

The formation of a third ring by a PPA-catalyzed intramolecular cyclization of the malononitrile derivative (683) gives a single product (684), in contrast to the mixture obtained from a similar reaction on the thiochromanone (76JHC123). 

If a thiochromanone is the starting system for sulfilimine preparation, another mode of reaction becomes available, namely ring expansion or contraction with insertion of the sulfilimine nitrogen (Scheme 8) (80TL533). The nature of the product is defined by the relative propensity for Michael addition (ring expansion) or thiooxime formation (ring contraction) to occur. 

ZC91). A related reaction, with even more curious consequence, is shown in equation (33) (73CJC839). However, aldol condensation of thiochromanones with aldehydes in the presence of weak bases proceeds exactly as for carbocyclic systems (79MI22501). 

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